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ectonucleoside triphosphate diphosphohydrolase 1

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Target id: 2888

Nomenclature: ectonucleoside triphosphate diphosphohydrolase 1

Abbreviated Name: NTPDase-1

Systematic Nomenclature: CD39

Family: Hydrolases & Lipases

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 2 510 10q24.1 ENTPD1 ectonucleoside triphosphate diphosphohydrolase 1
Mouse 2 510 19 34.25 cM Entpd1 ectonucleoside triphosphate diphosphohydrolase 1
Rat 2 511 1q54 Entpd1 ectonucleoside triphosphate diphosphohydrolase 1
Gene and Protein Information Comments
Several transcript variants encoding different isoforms of human ENTPD1 (CD39) have been reported. We provide details for isoform 1. For the mouse gene we show isoform 2, which corresponds in length to human isoform 1.
Previous and Unofficial Names Click here for help
NTPDase-1 | SPG64 | ATPDase | Ecto-ATPDase 1 | Ecto-apyrase
Database Links Click here for help
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
RefSeq Nucleotide
RefSeq Protein
Enzyme Reaction Click here for help
EC Number:
Description Reaction Reference
Hydrolyzes NTPs to nucleotide monophosphates (NMPs) A nucleoside 5'-triphosphate + 2 H2O <=> a nucleoside 5'-phosphate + 2 phosphate

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Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
PSB-0963 Small molecule or natural product Hs Inhibition 5.6 pKi 2
pKi 5.6 (Ki 2.59x10-6 M) [2]
ARL 67156 Small molecule or natural product Ligand has a PDB structure Rn Inhibition 4.6 pKi 4
pKi 4.6 (Ki 2.7x10-5 M) [4]
View species-specific inhibitor tables
Key to terms and symbols Click column headers to sort
Antibody Sp. Action Value Parameter Reference
perenostobart Peptide Immunopharmacology Ligand Hs Inhibition - - 7
Immunopharmacology Comments
Via the conversion of ADP/ATP to AMP (CD39; ENTPD1) and AMP to adenosine (CD73; NT5E) these ectonucleotidase enzymes are crucial to the regulation of purinergic signals delivered to immune cells [1]. CD39 is emerging as a promising molecular target in oncology [3]. Upregulated CD39 expression has been identified as a marker of cell exhaustion in tumour-infiltrating CD8+ T cells [6]. Inhibition of the CD39-CD73-adenosine pathway selectively inhibits Treg function and mitigates adenosine-induced immunosuppression in the tumour environment. Increased adenosine levels are reported in tumours, and drives a shift to an anti-inflammatory environment which can promote tumour growth [13]. Increasing evidence validates both of these enzymes as potential druggable targets in cancer [3,10,12].
Innate Pharma has an ongoing anti-CD39 programme (IPH52) in preclinical development (Feb 2017).
Immuno Process Associations
Immuno Process:  Cytokine production & signalling
Tissue Distribution Click here for help
Lymphoid tissue: some paracortical lymphocytes and most macrophages and dendritic cells express CD39, but it is not significantly expressed by germinal center cells.
Species:  Human
Technique:  Immunohistochemistry
References:  11
CD39 is expressed on activated NK cells, B cells, subsets of T cells, and T cell clones, but not on these cells in the resting state.
Species:  Human
Technique:  Immunohistochemistry
References:  11
CD39 is expressed in endothelial tissues and some endothelial cell lines in vitro.
Species:  Human
Technique:  Immunohistochemistry
References:  11
Physiological Functions Click here for help
CD39 engagement by anti-CD39 antibody on adhesion deficient leukocytes promotes adhesion, suggesting a role for CD39 signalling in the regulation of adhesion.
Species:  Human
Tissue:  Patient-derived leukocytes
References:  11
ENTPD1 plays a role in hemostasis and thrombotic reactions.
Species:  Mouse
References:  9
Physiological Consequences of Altering Gene Expression Click here for help
Overexpression of CD39 and a high CD39(+)/CD8(+) ratio in gastric cancer cells is associated with poor prognosis.
Species:  Human
Tissue:  Cells and tissue derived from gastric cancer patients
Technique:  Immunohistochemistry.
References:  5
Cd39-deficient mice have prolonged bleeding times, with platelet hypofunction and fibrin deposits at multiple organ sites.
Species:  Mouse
Tissue:  Cardiac tissue and platelets from Cd39-deficient mice, and in vivo observations.
Technique:  Homologous recombination
References:  9
Deletion of Entpd1 causes hepatic insulin resistance (impaired glucose tolerance), characterised by altered hepatic glucose metabolism and a proinflammatory phenotype (increased serum interleukin-1β, interleukin-6, interferon γ, and tumor necrosis factor α).
Species:  Mouse
Tissue:  Liver, blood
References:  8


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1. Antonioli L, Pacher P, Vizi ES, Haskó G. (2013) CD39 and CD73 in immunity and inflammation. Trends Mol Med, 19 (6): 355-67. [PMID:23601906]

2. Baqi Y, Lee SY, Iqbal J, Ripphausen P, Lehr A, Scheiff AB, Zimmermann H, Bajorath J, Müller CE. (2010) Development of potent and selective inhibitors of ecto-5'-nucleotidase based on an anthraquinone scaffold. J Med Chem, 53 (5): 2076-86. [PMID:20146483]

3. Bastid J, Cottalorda-Regairaz A, Alberici G, Bonnefoy N, Eliaou JF, Bensussan A. (2013) ENTPD1/CD39 is a promising therapeutic target in oncology. Oncogene, 32 (14): 1743-51. [PMID:22751118]

4. Brunschweiger A, Iqbal J, Umbach F, Scheiff AB, Munkonda MN, Sévigny J, Knowles AF, Müller CE. (2008) Selective nucleoside triphosphate diphosphohydrolase-2 (NTPDase2) inhibitors: nucleotide mimetics derived from uridine-5'-carboxamide. J Med Chem, 51 (15): 4518-28. [PMID:18630897]

5. Cai XY, Wang XF, Li J, Dong JN, Liu JQ, Li NP, Yun B, Xia RL. (2015) Overexpression of CD39 and high tumoral CD39(+)/CD8(+) ratio are associated with adverse prognosis in resectable gastric cancer. Int J Clin Exp Pathol, 8 (11): 14757-64. [PMID:26823801]

6. Canale FP, Ramello MC, Núñez N, Araujo Furlan CL, Bossio SN, Gorosito Serrán M, Tosello Boari J, Del Castillo A, Ledesma M, Sedlik C et al.. (2018) CD39 Expression Defines Cell Exhaustion in Tumor-Infiltrating CD8+ T Cells. Cancer Res, 78 (1): 115-128. [PMID:29066514]

7. Chappel S, Lake A, Warren M, Dulak A, Devereaux E, Holland PM, Zaidi T, Rausch M, Prinz B, Nielson NP et al.. (2020) Antibodies that bind CD39 and uses thereof. Patent number: US10738128B2. Assignee: Surface Oncology Inc. Priority date: 14/03/2018. Publication date: 11/08/2020.

8. Enjyoji K, Kotani K, Thukral C, Blumel B, Sun X, Wu Y, Imai M, Friedman D, Csizmadia E, Bleibel W et al.. (2008) Deletion of cd39/entpd1 results in hepatic insulin resistance. Diabetes, 57 (9): 2311-20. [PMID:18567823]

9. Enjyoji K, Sévigny J, Lin Y, Frenette PS, Christie PD, Esch 2nd JS, Imai M, Edelberg JM, Rayburn H, Lech M et al.. (1999) Targeted disruption of cd39/ATP diphosphohydrolase results in disordered hemostasis and thromboregulation. Nat Med, 5 (9): 1010-7. [PMID:10470077]

10. Häusler SF, Del Barrio IM, Diessner J, Stein RG, Strohschein J, Hönig A, Dietl J, Wischhusen J. (2014) Anti-CD39 and anti-CD73 antibodies A1 and 7G2 improve targeted therapy in ovarian cancer by blocking adenosine-dependent immune evasion. Am J Transl Res, 6 (2): 129-39. [PMID:24489992]

11. Kansas GS, Wood GS, Tedder TF. (1991) Expression, distribution, and biochemistry of human CD39. Role in activation-associated homotypic adhesion of lymphocytes. J Immunol, 146 (7): 2235-44. [PMID:1672348]

12. Stagg J. (2012) The double-edge sword effect of anti-CD73 cancer therapy. Oncoimmunology, 1 (2): 217-218. [PMID:22720247]

13. Wang L, Fan J, Thompson LF, Zhang Y, Shin T, Curiel TJ, Zhang B. (2011) CD73 has distinct roles in nonhematopoietic and hematopoietic cells to promote tumor growth in mice. J Clin Invest, 121 (6): 2371-82. [PMID:21537079]

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